The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.
As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.
CHEST
Dr. Benjamin T. Wilson
Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).
A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).
Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.
CHEST
Dr. Abhimanyu Chandel
It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.
The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.
Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.